RESUMO
BACKGROUND: Helicobacter pylori plays a decisive role in the pathogenesis of gastric marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT), and eradication therapy has become a widely accepted initial treatment of stage I disease. OBJECTIVE: To determine the long term outcome of patients undergoing exclusive H pylori eradication therapy. DESIGN: A prospective series of patients with newly diagnosed marginal zone B cell lymphoma of MALT. SETTING: Multicentre study in Germany and Austria. PATIENTS: Ninety five patients; 90 of these (five lost to follow up) with a mean age of 54.3 (27-85) years were followed up for at least 12 months. INTERVENTION: Complete staging work up revealing stage I disease and H pylori infection. Patients received triple therapy (OMC: omeprazole 20 mg twice daily, metronidazole 400 mg twice daily, and clarithromycin 250 mg twice daily; or OAC: omeprazole 20 mg twice daily, amoxycillin 1000 mg twice daily, and clarithromycin 500 twice daily) for one week. RESULTS: Median follow up was 44.6 (12-89) months. H pylori was successfully eradicated in 88 patients (98%); in two patients eradication therapy failed. Long term outcome was characterised by complete regression of lymphoma in 56 patients (62%), minimal residual disease in 17 patients (18%), partial remission in 11 patients (12%), no change in four patients (4%), and progressive disease in two patients (2%). Four patients with complete remission relapsed after 6, 8, 8, and 15 months, one revealing reinfection by H pylori. Regression rate was higher in stage I1 disease compared with stage I2, as diagnosed by endoscopic ultrasound. CONCLUSION: The majority of patients with low grade gastric MALT lymphoma treated by exclusive H pylori eradication have a favourable long term outcome, offering a real chance of cure.
Assuntos
Anti-Infecciosos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Linfoma de Zona Marginal Tipo Células B/microbiologia , Neoplasias Gástricas/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Amoxicilina/uso terapêutico , Claritromicina/uso terapêutico , Quimioterapia Combinada , Feminino , Seguimentos , Infecções por Helicobacter/complicações , Humanos , Masculino , Metronidazol/uso terapêutico , Pessoa de Meia-Idade , Omeprazol/uso terapêutico , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Endoscopic ultrasound (EUS) is considered the best technique for local staging of primary gastric lymphomas. Its role in the follow up of patients with gastric lymphoma following organ conserving strategies has not been established. AIM: To compare endosonographic response assessment with results of histological evaluation. PATIENTS AND METHODS: Thirty three patients with primary gastric lymphomas underwent pretreatment EUS and were followed endosonographically every 3-6 months after administration of organ conserving treatment modalities. A wall thickness of Assuntos
Endossonografia
, Linfoma de Zona Marginal Tipo Células B/diagnóstico por imagem
, Neoplasias Gástricas/diagnóstico por imagem
, Adolescente
, Adulto
, Idoso
, Idoso de 80 Anos ou mais
, Feminino
, Seguimentos
, Humanos
, Linfoma de Zona Marginal Tipo Células B/patologia
, Linfoma de Zona Marginal Tipo Células B/terapia
, Masculino
, Pessoa de Meia-Idade
, Estadiamento de Neoplasias
, Neoplasias Gástricas/patologia
, Neoplasias Gástricas/terapia
, Fatores de Tempo
RESUMO
The incidence of celiac disease has increased considerably during the last two decades. Celiac Disease is now diagnosed in adults at least as frequently as in children. A prevalence of about 1:200 seems reasonable in central Europe. Besides the typical symptomatic presentation, silent, latent and potential celiac disease are found. Oligo- to asymptomatic courses (silent celiac disease) are increasingly found in all age groups. Endomysial antibodies and tissue-transglutaminase antibodies are sensitive and specific for about 95% of celiac patients. However, the final diagnosis is only done by a - mostly endoscopical - biopsy from the distal part of the duodenum, demonstrating hyperplastic villous atrophy of the mucosa with increased numbers of intraepithelial lymphocytes. The biopsies should be classified histologically according to the modified Marsh criteria. Increased prevalence in family members (10 to 15%) and in associated diseases (e.g. diabetes mellitus) lead to the recommendation of active screening in populations at risk. Although the clinical symptoms are rather variable and different, the response to a lifelong strict gluten free diet is nearly 100%. So-called refractory celiac disease is very rare. There are numerous associated diseases as dermatitis herpetiformis, diabetes mellitus type I, thyroid and neurologic diseases. The most frequent complications are retardation of growth in childhood, early onset osteoporosis, and an increased risk of abortions. The most severe complication is intestinal lymphoma. Especially patients with late diagnosis and bad dietary adherence are at risk. A regular follow-up of patients, rather with antibody tests than with duodenal biopsies is recommended to test and secure dietary compliance.
Assuntos
Doença Celíaca/diagnóstico , Adolescente , Adulto , Áustria , Autoanticorpos/sangue , Biópsia , Doença Celíaca/dietoterapia , Doença Celíaca/epidemiologia , Doença Celíaca/genética , Estudos Transversais , Endoscopia Gastrointestinal , Predisposição Genética para Doença/genética , Testes Genéticos , Glutens/administração & dosagem , Glutens/efeitos adversos , Humanos , Mucosa Intestinal/patologiaRESUMO
BACKGROUND: There is much controversy as to whether or not treatment of Helicobacter pylori reduces the occurrence of peptic ulcers during therapy with a non-steroidal anti-inflammatory drug (NSAID). AIM: To assess the efficacy of triple therapy or omeprazole on the occurrence of diclofenac associated ulcers in H pylori positive patients. METHODS: This was a randomised, double blind, placebo controlled, multicentre trial in H pylori positive patients requiring NSAID therapy who had no past or current peptic ulcer. They received diclofenac 50 mg twice daily for five weeks in combination with one of the four randomly assigned treatments: anti-H pylori treatment for one week (omeprazole 20 mg+clarithromycin 500 mg+amoxicillin 1 g, all twice daily) followed by placebo for four weeks (OAC-P); anti-H pylori treatment for one week followed by antisecretory treatment with omeprazole 20 mg once daily for four weeks (OAC-O); omeprazole 20 mg once daily for five weeks (O-O); or placebo for five weeks (P-P). Patients were endoscoped before and after treatment. RESULTS: Data from 660 patients were included in an intention to treat analysis. The occurrence of peptic ulcers in the four treatment groups during the study period was: 1.2% for OAC-P, 1.2% for OAC-O, 0% for O-O, and 5.8% for P-P (p<0.05 between placebo and all active treatment groups). Patients who received active treatment developed therapy requiring dyspeptic symptoms less frequently than those who received placebo (p<0.05 between placebo and all active treatment groups). CONCLUSIONS: In H pylori infected patients, all three active therapies reduced the occurrence of NSAID associated peptic ulcer and dyspeptic symptoms requiring therapy.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Antiulcerosos/uso terapêutico , Diclofenaco/efeitos adversos , Dispepsia/prevenção & controle , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Omeprazol/uso terapêutico , Úlcera Péptica/prevenção & controle , Adulto , Amoxicilina/uso terapêutico , Claritromicina/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada/uso terapêutico , Dispepsia/induzido quimicamente , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Úlcera Péptica/induzido quimicamente , Resultado do TratamentoRESUMO
BACKGROUND: Recent data suggest that chemotherapy with the cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) regimen is a highly effective treatment for localised primary gastric lymphoma of diffuse large B-cell histology (DLBCL). We have reported that the large majority of patients achieve complete remission (CR) following three cycles of treatment, and now provide an updated series with special emphasis on patients receiving only short-term chemotherapy. PATIENTS AND METHODS: All patients with a histologically verified diagnosis of gastric DLBCL in stages EI and EII(1) undergoing chemotherapy with the CHOP regimen were evaluated. Data analysed included clinical stage, histology [presence of an additional mucosa-associated lymphoid tissue (MALT) component], evidence of Helicobacter pylori infection, H. pylori eradication, time to CR, survival and regular restaging (i.e. after three and six cycles, respectively). RESULTS: A total of 37 patients with DLBCL of the stomach with localised disease were identified, five of whom also had a MALT component. Twenty-two patients presented with stage EI and 15 with stage EII(1) disease. All patients were given chemotherapy as sole management of their lymphoma; 36 patients received CHOP, while one patient was given CHOP along with rituximab. Thirty-two (86%) achieved a CR after a maximum of three cycles, while only four patients had to be given six cycles for CR. In total, nine of 37 patients (24%) discontinued therapy earlier than scheduled: one patient received one cycle, two received two, six received three and one patient received four cycles. Two of these patients stopped treatment due to toxicity, i.e. protracted thrombocytopenia or chemotherapy extravasation. One additional patient died after one cycle of treatment; autopsy disclosed no signs of remaining lymphoma. Three patients have died after a median follow-up of 39 months (including the one patient who discontinued therapy after one cycle of treatment), while the remaining 34 patients are alive without evidence of disease. Twenty-four out of 37 patients (65%) had also undergone H. pylori eradication (including six of nine patients receiving only short-term treatment). CONCLUSIONS: DLBCL of the stomach appears to be a highly chemosensitive disease. Our data question the need for full-term CHOP treatment in patients achieving CR upon first follow-up. However, recent data suggest that additional H. pylori eradication might have contributed to the excellent results achieved in our series.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Linfoma de Zona Marginal Tipo Células B/patologia , Prednisona/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Vincristina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Estudos de Coortes , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Linfoma de Zona Marginal Tipo Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Gástricas/mortalidade , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Gastric MALT-lymphoma is thought to be related to chronic antigenic stimulation provided by Helicobacter pylori (HP). As clonal expansion of gastric B cells not related to HP has been demonstrated in patients with autoimmune disease (AD), we have analysed whether AD adversely influences response of MALT-lymphoma following HP-eradication. PATIENTS AND METHODS: Retrospective analysis of all patients with early stage gastric MALT-lymphoma treated with HP-eradication was performed. The presence of AD was evaluated by personal questioning for specific symptoms and serologically by analysis of rheumatoid factor, antinuclear antibodies and thyroid autoantibodies. RESULTS: A total of 22 patients were identified receiving only antibiotic treatment for initial management, and six presented with an autoimmune condition: three had Sjögren's syndrome, one polymyalgia rheumatica, one autoimmune thyroiditis along with psoriasis, and one patient had only autoimmune thyroiditis. Successful eradication of HP was achieved in all patients, and 15 of 22 patients (68%) achieved complete response of the lymphoma, while none out of the six patients with an autoimmune disorder responded to HP-eradication. CONCLUSION: Apart from questioning the role of HP in the development of lymphoma in such patients, these results suggest that patients with autoimmune disease might not be optimal candidates for HP-eradication even in case of early stage lymphoma.
Assuntos
Antibacterianos/uso terapêutico , Doenças Autoimunes/complicações , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Linfoma de Zona Marginal Tipo Células B/microbiologia , Neoplasias Gástricas/microbiologia , Idoso , Feminino , Helicobacter pylori/isolamento & purificação , Humanos , Linfoma de Zona Marginal Tipo Células B/imunologia , Linfoma de Zona Marginal Tipo Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Resultado do TratamentoRESUMO
AIM: To test the hypothesis that Helicobacter pylori eradication alone can reduce the incidence of gastric cancer in a subgroup of individuals with an increased risk for this fatal disease. METHODS: It is a prospective, randomized, double blind, placebo controlled multinational multicenter trial. Men between 55 and 65 years of age with a gastric cancer phenotype of Helicobacter pylori gastritis are randomized to receive a 7 day course of omeprazole 2 X 20mg, clarithromycin 2 X 500mg, and amoxicillin 2 X 1g for 7 days, or omeprazole 2 X 20mg plus placebo. Follow-up endoscopy is scheduled 3 months after therapy, and thereafter in one-year intervals. Predefined study endpoints are gastric cancer, precancerous lesions (dysplasia, adenoma), other cancers, and death. RESULTS: Since March 1998, 1524 target patients have been screened, 279 patients (18.3%) had a corpus dominant type of H. pylori gastritis, and 167 of those were randomized (58.8%). In the active treatment group (r = 86), H. pylori infection infection was cured in 88.9% of patients. Currently, the cumulative follow-up time is 3046 months (253.38 patient years, median follow up 16 months). So far, none of the patients developed gastric cancer or any precancerous lesion. Three (1.8%) patients reached study endpoints other than gastric cancer. CONCLUSION: Among men between 55 and 65 years of age, the gastric cancer phenotype of H. pylori gastritis appears to be more common than expected. Further follow up and continuing recruitment are necessary to fulfil the main aim of the study.
Assuntos
Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Claritromicina/uso terapêutico , Gastrite/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Omeprazol/uso terapêutico , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/prevenção & controle , Quimioterapia Combinada , Gastrite/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND & AIMS: Appropriate management of primary gastric lymphoma is controversial. This prospective, multicenter study aimed to evaluate the accuracy of endoscopic biopsy diagnosis and clinical staging procedures and assess a treatment strategy based on Helicobacter pylori status and tumor stage and grade. METHODS: Of 266 patients with primary gastric B-cell lymphoma, 236 with stages EI (n = 151) or EII (n = 85) were included in an intention-to-treat analysis. Patients with H. pylori-positive stage EI low-grade lymphoma underwent eradication therapy. Nonresponders and patients with stage EII low-grade lymphoma underwent gastric surgery. Depending on the residual tumor status and predefined risk factors, patients received either radiotherapy or no further treatment. Patients with high-grade lymphoma underwent surgery and chemotherapy at stages EI/EII, complemented by radiation in case of incomplete resection. RESULTS: Endoscopic-bioptic typing and grading and clinical staging were accurate to 73% and 70%, respectively, based on the histopathology of resected specimens. The overall 2-year survival rates for low-grade lymphoma did not differ in the risk-adjusted treatment groups, ranging from 89% to 96%. In high-grade lymphoma, patients with complete resection or microscopic tumor residuals had significantly better survival rates (88% for EI and 83% for EII) than those with macroscopic tumor residues (53%; P < 0.001). CONCLUSIONS: There is a considerable need for improvement in clinical diagnostic and staging procedures, especially with a view toward nonsurgical treatment. With the exception of eradication therapy in H. pylori-positive low-grade lymphoma of stage EI and the subgroup of locally advanced high-grade lymphoma, resection remains the treatment of choice. However, because there is an increasing trend toward stomach-conserving therapy, a randomized trial comparing cure of disease and quality of life with surgical and conservative treatment is needed.
Assuntos
Biópsia/métodos , Biópsia/normas , Endoscopia/normas , Linfoma de Células B/patologia , Linfoma de Células B/terapia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Terapia Combinada , Gastrectomia , Infecções por Helicobacter/complicações , Helicobacter pylori , Humanos , Linfoma de Células B/microbiologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias/normas , Estudos Prospectivos , Radioterapia , Neoplasias Gástricas/microbiologiaRESUMO
Helicobacter pylori (H.p.) causes active chronic gastritis in nearly all infected patients. Cytotoxic factors elaborated by H.p. as well as autoimmune cell damage from the abundant inflammatory response contribute to gastric epithelial cell injury. Antrum gastritis increases gastrin release. The impact of H.p.-infection on gastric acid physiology is complex and usually results in increased gastric acid secretion in duodenal ulcer patients and diminished acid output in patients with gastric cancer. Multiple clinical outcomes including asymptomatic gastritis, duodenal ulcer, gastric ulcer, gastric carcinoma and gastric MALT lymphoma are associated with H.p.-infection. Differences in disease manifestation seem to result from a complex interaction of bacterial virulence, host factors as well as environmental factors. The acid-secretory ability of the infected individual seems to be the main variable determining outcome: Patients with high acid production typically develop antrum-predominant gastritis and are at an increased risk for duodenal ulcer. In contrast patients with low gastric acid secretion frequently develop pangastritis, which may progress to chronic atrophic gastritis and carcinoma.
Assuntos
Infecções por Helicobacter/fisiopatologia , Helicobacter pylori , Úlcera Duodenal/microbiologia , Gastrite/microbiologia , Gastrite/fisiopatologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/imunologia , Humanos , Linfoma de Zona Marginal Tipo Células B/microbiologia , Úlcera Gástrica/microbiologiaRESUMO
Lymphoma of the mucosa-associated lymphoid tissue (MALT) type usually arises in MALT acquired through chronic antigenic stimulation triggered by persistent infection and/or autoimmune processes. Due to specific ligand-receptor interactions between lymphoid cells and high-endothelial venules of MALT, both normal and neoplastic lymphoid cells display a pronounced homing tendency to MALT throughout the body. In the case of neoplastic disease these homing properties may be responsible for lymphoma dissemination among various MALT-sites. According to this concept, we have standardized staging procedures in all patients diagnosed with MALT-type lymphoma. All patients with MALT-type lymphoma underwent standardized staging procedures before treatment. Staging included ophthalmologic examination, otolaryngologic investigation, gastroscopy with multiple biopsies, endosonography of the upper gastrointestinal tract, enteroclysis, colonoscopy, computed tomography of thorax and abdomen and bone marrow biopsy. Biopsy was performed in all lesions suggestive for lymphomatous involvement, and evaluation of all biopsy specimens was performed by a reference pathologist. 35 consecutive patients with histologically verified MALT-type lymphoma were admitted to our department. Twenty-four patients (68%) had primary involvement of the stomach, five (15%) had lymphoma of the ocular adnexa, three (8.5%) had lymphoma of the parotid, and three (8,5%) of the lung. Lymph-node involvement corresponding to stage EII disease was found in 13 patients (37%), only one patient with primary gastric lymphoma had local and supradiaphragmatic lymph-node involvement (stage EIII). Bone marrow biopsies were negative in all patients. Overall, eight of 35 patients (23%) had simultaneous biopsy-proven involvement of two MALT-sites: one patient each had lymphoma of parotid and lacrimal gland, conjunctiva and hypopharynx, conjunctiva and skin, lacrimal gland and lung, stomach and colon, and stomach and lung. The remaining two patients had bilateral parotideal lymphoma. Staging work-up was negative for lymph-node involvement in all of these eight patients. The importance of extensive staging in MALT-type lymphoma is emphasized by the demonstration of multiorgan involvement in almost a quarter of patients. In addition, our data suggest that extra-gastrointestinal MALT-type lymphoma more frequently occurs simultaneously at different anatomic sites than MALT-type lymphoma involving the GI-tract.
Assuntos
Linfoma de Zona Marginal Tipo Células B/patologia , Neoplasias Oculares/patologia , Humanos , Neoplasias Pulmonares/patologia , Metástase Linfática , Linfoma não Hodgkin/patologia , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/patologia , Neoplasias Parotídeas/patologia , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: Surgical intervention and combined modality treatment including radiation and chemotherapy have been studied widely in patients with high grade gastric B-cell lymphoma, whereas to the authors' knowledge the role of chemotherapy alone in patients with localized disease has not been investigated extensively. METHODS: Twenty-five consecutive patients with primary high grade gastric B-cell lymphoma of localized modified Ann Arbor Stages IE and IIE were studied prospectively at the study institution. Patients age < 75 years (n = 17; age range, 41-75 years) were given a standard regimen comprised of doxorubicin, cyclophosphamide, vincristine, and prednisone (CHOP), whereas patients age > 75 years (n = 8; age range, 82-93 years) were treated at a reduced dose. Restaging was performed after 3 and 6 cycles, followed by every 3 months for the first 2 years, and every 6 months thereafter. RESULTS: A total of 123 cycles were administered to the study patients, with the median number of 6 cycles per patient (range, 1-9 cycles). At a median follow-up of 24 months (range, 1.5-87+ months), 22 patients were alive without evidence of disease and 3 patients had died (1 patient death was treatment-related). Twenty-four patients who were considered evaluable achieved a complete remission, 21 patients after 3 cycles and the remaining 3 patients after 6 cycles of treatment. Side effects generally were manageable, with only one patient requiring premature discontinuation of treatment due to protracted thrombocytopenia after three courses of therapy, and tolerance was not different between the two age groups. No recurrences were observed at last follow-up. CONCLUSIONS: The authors believe that chemotherapy using the CHOP regimen is highly effective in the treatment of patients with localized primary high grade gastric lymphoma.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Estudos Prospectivos , Indução de Remissão , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Trombocitopenia/induzido quimicamente , Vincristina/administração & dosagemRESUMO
BACKGROUND: One-week low-dose triple therapy is currently considered the gold standard regimen for treatment of Helicobacter pylori infection. However, the mechanisms involved in the synergy between antibiotics and proton pump inhibitors are controversial. AIMS: To test the hypothesis that acid suppression represents the crucial mechanism by which the antibacterial activity of antibiotics can be enhanced, and to assess the impact of primary resistance on treatment outcome. METHODS: One hundred and twenty patients with H. pylori infection and duodenal ulcer, gastric ulcer or non-ulcer dyspepsia were randomly assigned to a 1 week course of either famotidine 80 mg b.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (FCM group; n = 60) or omeprazole 20 mg o.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (OCM group; n = 60). Gastroscopy was performed at baseline and 5 weeks after completion of treatment. H. pylori status was assessed by biopsy urease test, histology and culture. RESULTS: In the intention-to-treat analysis, eradication of H. pylori was achieved in 47 of 60 patients (78%; 95% CI: 66-88%) in the FCM group, compared to 44 of 60 patients (73%; 95% CI: 60-84%) in the OCM group (N.S.). Using per protocol analysis, eradication therapy was successful in 47 of 52 patients (90%; 95% CI: 79-97%) treated with FCM and 44 of 57 patients (77%; 95% CI: 64-87%) treated with OCM (N.S.). Primary metronidazole resistance was present in 27% and primary clarithromycin resistance in 8% of strains. Overall per protocol eradication rates in strains susceptible to both antibiotics and strains with isolated metronidazole resistance were 93% and 84%, respectively. No patient with clarithromycin resistance responded to treatment. CONCLUSIONS: High-dose famotidine and omeprazole, combined with clarithromycin and metronidazole, are equally effective for eradication of H. pylori. In 1-week low-dose triple therapy, metronidazole resistance has no major impact on eradication rates whereas clarithromycin resistance is associated with a poor treatment outcome.
Assuntos
Antibacterianos/uso terapêutico , Antiulcerosos/uso terapêutico , Claritromicina/uso terapêutico , Famotidina/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori , Metronidazol/uso terapêutico , Omeprazol/uso terapêutico , Adulto , Idoso , Antibacterianos/efeitos adversos , Antiulcerosos/efeitos adversos , Claritromicina/efeitos adversos , Combinação de Medicamentos , Resistência Microbiana a Medicamentos , Famotidina/efeitos adversos , Feminino , Humanos , Masculino , Metronidazol/efeitos adversos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Omeprazol/efeitos adversos , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/microbiologiaAssuntos
Gastrite/diagnóstico , Infecções por Helicobacter/diagnóstico , Helicobacter pylori , Neoplasias Gástricas/prevenção & controle , Adulto , Idoso , Áustria , Transformação Celular Neoplásica/patologia , Mucosa Gástrica/patologia , Gastrite/patologia , Gastroscopia , Alemanha , Infecções por Helicobacter/patologia , Humanos , Masculino , Programas de Rastreamento , Fatores de Risco , Neoplasias Gástricas/patologiaRESUMO
OBJECTIVES: The combination of a proton pump inhibitor (PPI) such as omeprazole with amoxicillin and clarithromycin constitutes one of the most effective treatments for the eradication of Helicobacter pylori. Nevertheless, the mechanisms of interaction between these drugs remain unclear. It has been shown that minimal inhibitory concentration values of both antibiotics are considerably lower at neutral pH levels than in an acid environment. Further, omeprazole possesses bacteriostatic activity. To evaluate the significance of these mechanisms we replaced omeprazole with famotidine, a drug which only suppresses acid production, but has no intrinsic antimicrobial activity. METHODS: We evaluated the efficacy of a 1-week course of famotidine 80 mg b.i.d., amoxicillin 1000 mg b.i.d. and clarithromycin 500 mg b.i.d. in a pilot study (20 patients), and then confirmed our results in a larger replication study (87 patients). A total of 107 patients with H. pylori-associated duodenal ulcer (n = 54), gastric ulcer (n = 14) or non-ulcer dyspepsia (n = 39) were included. Endoscopy was performed at baseline and 4-6 weeks after discontinuation of treatment. H. pylori status was assessed by the urease test and histology. RESULTS: H. pylori was successfully eradicated in 94 of 104 patients who completed the study (90.4%; CI 95%, 83.0-95.3%). By intention-to-treat analysis, the eradication rate was 87.9% (CI 95%, 80.1-93.4%). Ulcer healing was observed in 98.1% of duodenal ulcers and 92.9% of gastric ulcers (based on per-protocol analysis). Mild side effects that did not require termination of treatment were reported by seven patients (6.7%). CONCLUSION: A 1-week course of famotidine, amoxicillin and clarithromycin is a highly effective, simple and safe eradication regimen. Our data indicate that acid suppression is the crucial mechanism by which the activity of amoxicillin and clarithromycin against H. pylori is enhanced, whereas additional antimicrobial activity or other specific effects of PPIs seem to be less important.
Assuntos
Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Famotidina/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Penicilinas/uso terapêutico , Adulto , Idoso , Quimioterapia Combinada , Úlcera Duodenal/tratamento farmacológico , Úlcera Duodenal/microbiologia , Feminino , Humanos , Macrolídeos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/microbiologia , Resultado do TratamentoRESUMO
BACKGROUND: Blood group Lewis(b) antigens mediate Helicobacter pylori attachment to gastric mucosa with attachment being particularly strong in subjects with ABH blood group O. AIMS: To determine whether H pylori colonisation or the occurrence of gastric mucosa associated lymphoid tissue (MALT) lymphomas might be related to gastric Lewis(b) expression or occurrence of particular ABH blood groups on gastric mucosa. PATIENTS: Gastric resection specimens from 89 cases with gastric MALT lymphoma and gastric mucosal biopsy specimens from 95 patients undergoing upper endoscopy due to upper gastrointestinal complaints, including five cases with gastric MALT lymphoma, were studied. METHODS: H pylori was visualised with the Warthin-Starry stain. Immunostaining (Lewis(b), Lewis(a), A, B) was performed by applying a three step immunoperoxidase technique and indirect immunofluorescence staining on formalin fixed and paraffin wax embedded tissue. In 40 patients red blood cell Lewis phenotype and ABH blood groups were additionally determined by haemagglutination assay. RESULTS: Gastric surface epithelial cells showed an immunoreactivity to blood groups A, B, and AB in 80 (43.5%), 22 (12%), and 11 (6%) cases respectively and no immunoreactivity to any of these blood group substances (blood group O) in 71 (38.5%) patients. Lewis(b) expression of all gastric surface epithelial cells (secretor status) was found in 130 (70.7%) cases. Lewis(a) expression of all gastric surface epithelial cells (non-secretor status) was found in 36 (19.6%) cases, secretor status remained unclassified in 18 (9.8%) patients. Colonisation with H pylori was found in 134 (72.8%) cases. The occurrence of H pylori was neither significantly associated with secretor status nor with certain ABH blood groups. The infiltration of gastric mucosa with MALT lymphoma was highly significantly associated with H pylori colonisation (p < 0.0003) but neither with secretor status nor with certain ABH blood groups. There was no inter-relation between secretor status or ABH blood groups and type, stage, grade of, and survival after MALT lymphoma. CONCLUSION: This study failed to show an inter-relation between secretor status or particular ABH blood groups and either H pylori infection or the occurrence of gastric MALT lymphomas.
Assuntos
Sistema ABO de Grupos Sanguíneos , Mucosa Gástrica/metabolismo , Infecções por Helicobacter/sangue , Helicobacter pylori/fisiologia , Antígenos do Grupo Sanguíneo de Lewis , Linfoma de Zona Marginal Tipo Células B/sangue , Aderência Bacteriana , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Humanos , Linfoma de Zona Marginal Tipo Células B/microbiologia , Linfoma de Zona Marginal Tipo Células B/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND & AIMS: In patients with Wilson's disease presenting with liver involvement, the correct diagnosis is often missed or delayed. The aim of this study was to find an algorithm for diagnosis of this difficult patient group. METHODS: Clinical and laboratory findings of 55 patients with Wilson's disease were evaluated at diagnosis before treatment. Presenting symptom was chronic liver disease in 17 patients, fulminant hepatic failure in 5 patients, hemolysis in 3 patients, and neurological disease in 20 patients, and 10 patients were detected by family screening (siblings). Evaluation included neurological and ophthalmologic examination, routine laboratory tests, and parameters of copper metabolism including liver copper content in 43 liver biopsy specimens. RESULTS: In the whole group, serum ceruloplasmin level was <20 mg/dL in 73%, urinary copper excretion was increased in 88%, and liver copper content was elevated in 91% at diagnosis. Kayser-Fleischer rings were detected in 55%. In contrast to patients with neurological disease (90% Kayser-Fleischer rings, 85% low ceruloplasmin), only 65% of patients presenting with liver disease were diagnosed by these typical findings. Ceruloplasmin levels were lower in patients with Kayser-Fleischer rings or with neurological disturbances than in patients without these symptoms. CONCLUSIONS: The commonly used clinical and laboratory parameters are not sufficient to exclude the diagnosis of Wilson's disease in patients with liver disease of unknown origin.
Assuntos
Algoritmos , Degeneração Hepatolenticular/diagnóstico , Adolescente , Biópsia , Ceruloplasmina/análise , Criança , Cobre/metabolismo , Diagnóstico Diferencial , Feminino , Degeneração Hepatolenticular/genética , Humanos , Fígado/química , Fígado/patologia , Hepatopatias/diagnóstico , MasculinoRESUMO
AIM: To study the effect of prokinetic treatment with cisapride in patients with constipation-predominant irritable bowel syndrome. PATIENTS AND METHODS: Ninety-six patients were randomly assigned to treatment with either cisapride 5 mg three times daily or placebo three times daily for a period of 12 weeks. The dosage could be doubled after 4 weeks. Presence of the target symptoms abdominal pain, constipation and abdominal bloating was an obligatory criterion for inclusion in the study. RESULTS: After 12 weeks of treatment, 31%, 56% and 27% of the cisapride treated patients were found to be without the three target symptoms (P < 0.05). The corresponding percentages for the placebo-treated patients were 31%, 58% and 19%, respectively, (P < 0.05). The visual analogue scale (VAS) symptom scores assessed by the patients for global rating of bowel disease, general well-being and frequency of stool passage improved significantly within each treatment group (P < 0.05). Evaluation of efficacy parameters using intention-to-treat analysis showed no statistically significant differences between the groups. Using efficacy analysis, the difficulty of stool passage showed a significantly higher improvement with cisapride (P < or = 0.05). CONCLUSIONS: These results indicate that cisapride is not superior to placebo in the treatment of constipation and abdominal discomfort as components of irritable bowel syndrome. It may, however, be of use in improving the difficulty of stool passage.
Assuntos
Dor Abdominal/tratamento farmacológico , Doenças Funcionais do Colo/tratamento farmacológico , Constipação Intestinal/tratamento farmacológico , Piperidinas/uso terapêutico , Dor Abdominal/etiologia , Adolescente , Adulto , Idoso , Cisaprida , Doenças Funcionais do Colo/complicações , Constipação Intestinal/etiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piperidinas/efeitos adversosRESUMO
Recent studies have identified the integrin alpha 4 beta 7 as a mucosal homing receptor that mediates lymphocyte migration to the intestinal mucosa by binding to MAdCAM-1, a vascular recognition molecule (addressin) selectively expressed on mucosal endothelium. In the present study, we have assessed the expression of alpha 4 beta 7 on B- and T-cell non-Hodgkin's lymphomas of different primary localization and on related normal lymphocytes. Among B-lineage lymphomas, expression of alpha 4 beta 7 was present in the majority of cases of malignant lymphomatous polyposis of the intestine and low-grade lymphoma of the mucosa-associated lymphoid tissue/monocytoid B-cell lymphoma and in some cases of precursor B-cell lymphoma. CLL/small lymphocytic lymphoma, (nodal) mantle cell lymphoma, follicular center cell lymphoma, Burkitt's lymphoma, and diffuse large B-cell lymphoma were virtually always alpha 4 beta 7 negative, as was the case when localized in the mucosa-associated lymphoid tissue. The normal B cells of the follicle mantles and part of the B cells of the extrafollicular B-cell compartment of lymphoid tissues expressed moderate levels of alpha 4 beta 7. By contrast, follicular center cells were alpha 4 beta 7 negative. Among T-lineage lymphomas, expression of alpha 4 beta 7 was also strongly related to the primary localization; in mucosal, nodal, and cutaneous T cell lymphomas the percentage of positive cases was 56%, 17%, and 0%, respectively. All cases of precursor T-cell lymphoma were alpha 4 beta 7 negative. High expression of alpha 4 beta 7 was found on a subset of peripheral blood memory T cells as well as on lymphocytes in the intestinal mucosa. We conclude that non-Hodgkin's lymphomas that are related to mucosa-associated B- and T-lymphocyte populations selectively express the mucosal homing receptor alpha 4 beta 7. The presence of this receptor underscores their distinctive character and may play an important role in determining their characteristic mucosal dissemination pattern.